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dc.contributor.authorSturgis, LaShon C.
dc.date.accessioned2021-05-02T21:26:48Z
dc.date.available2021-05-02T21:26:48Z
dc.date.issued2007
dc.identifier.urien
dc.identifier.urihttp://hdl.handle.net/10675.2/624003
dc.description.abstractAngiotensin II (Ang II) is involved critically in the development and maintenance of hypertension in both human and animal models. Ang II also is known to stimulate interleukin 6 (IL-6) release, and a recent study by our laboratory demonstrated that Ang II hypertension was attenuated in IL-6 knockout (KO) mice. These data suggest that IL-6 mediates part of the hypertensive actions of Ang II. In addition, Ang II also stimulates production and release of aldosterone, which also has hypertensive actions. Ang II also stimulates the proinflammatory cytokine tumor necrosis factor-alpha (TNF-a.), which can stimulate IL-6 secretion. Therefore, the aim of this project was to determine whether the dependence of Ang II hypertension on 11-6 is du.e to a direct link between Ang II and IL-6 or whether aldosterone and/or TNF-a. are important intermediate factors. In separate studies, we determined whether mineralocorticoid hypertension is IL-6 dependent, the role of IL-6 bioactivity verses IL-6 plasma concentration, and the role of TNF-a. in Ang II hypertension. Mineralocorticoid hypertension was induced by implanting a deoxycorticosterone acetate (DOCA) pellet (1 g/Kg) subcutaneously and giving all animals a solution of 1% sodium chlorid~ (NaCI) and 0.2 % potassium chloride (KCI) to dink for a 14 day experimental period. DOCA-salt treatment increased the mean arterial pressure (MAP) similarly by -30 mm . Hg in both the wr and IL-6 KO mice. However, DOCA-salt treatment did not increase plasma IL-6 concentration in wildtype {WT) mice nor did it increase . IL-6 bioavailability using a bioassay on day 14 of. treatment. There was,. however, a transient increase in plasma IL-6 concentration and bioactivity on day 7 of DOCA-salt treatment in the WT mice. Treating WT mice with Ang II and the mineralocorticoid receptor antagonist, spironolactone, significantly attenuated the Ang II mediated increase in plasma IL-6 concentration on day 7 and day 14 of treatment. Although we cannot explain why the IL-6 response to DOCA was not sustained through 14 days, together these data suggest that that aldosterone plays a role in the increase in plasma IL-6 concentration during Ang II hypertension. However the effect of IL-6 in mediating part of the Ang II hypertension appears d_ue to an interaction with Ang 11-mediated effects and not due to effects mediated by the mineralocorticoid receptor. Similarly, Ang II increased MAP by -30 mm Hg in both the·wr a·nd TN F-a. KO mice by day 14 of treatment. Moreover, which suggests that TN F-a. is not required for Ang II hypertension, Ang II treatment did not increase plasma levels of TN F-a. and TN F-a. infusion did not cause a sustained .increase in IL-6. These data suggest that Ang II may work through an aldosterone, but not TNF-a.- mediated, mechanism to increase plasma IL-6 concentration in Ang II hypertension, but that the role of IL-6 in mediating Ang II hypertension is due to interactions with Ang.ll receptor type 1 (AT1) dependent mechanisms on target tissues.en_US
dc.language.isoen_USen_US
dc.publisherAugusta Universityen_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.subjectHypertensionen_US
dc.subjectHormonesen_US
dc.titleMechanisms for the dependency of angiotensin II hypertension on interleukin-6en_US
dc.typeDissertationen_US
dc.contributor.departmentMedical College of Georgiaen_US
dc.description.advisorBrands, Michael W.
dc.description.committeeCannon, Joseph
dc.description.committeeDorrance, Anne
dc.description.committeePollock, David
dc.description.committeeWebb, Clinton
dc.description.degreeDoctor of Philosophyen_US
dc.embargoen
refterms.dateFOA2021-05-02T21:26:49Z


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